It is known that alkali metal organoamides such as lithium diisopropylamide are insoluble of themselves in purely hydrocarbon solvents at ordinary temperatures. Lithium diisopropyl amide has a solubility of 0.2N in heptane (C. W. Kamienski et al, J. Org. Chem. Vol. 30 p. 3498, 1965). It is further known that these hydrocarbon-insoluble alkali metal organoamides can be made soluble in ether-free hydrocarbon solutions by the addition of magnesium bis-diisopropylamide or soluble lithium amides. However, the presence of other organoamides is not always desirable, especially in the case where the particular lithium amide is a reactant and other lithium amides would similarly react and form undesirable side products.
Lithium amides are widely used as reagents in the preparation of pharmaceuticals and specialty chemicals. Lithium amides are particularly useful for the preparation of lithium acetylide compounds which are used to form acetylenic substituted organic compounds such as steroid fragrance intermediates. In order to form the lithium acetylide, acetylene is reacted with a lithium amide such as lithium diisopropyl amide just prior to reacting the newly formed lithium acetylide with the ketone or other reagent in the same reactor. All of these steps are performed below 0.degree. C. Usually, it is necessary to add an ether cosolvent such as tetrahydrofuran at this point to increase the limited solubility of the reagents and the subsequently formed lithium salt of the product from the reaction with the ketone. The lithium amide may be added as a preformed solution or it may be formed in the same reactor by reacting an alkyllithium such as n-butyllithium with an amine such as diisopropylamine. In either case, the lithium amide usually exhibits lower solubility than desired for maximum reactivity and yet there is a need to minimize the amount of solvents employed.
In order to increase the concentration of the lithium amide in the preformed solutions of the prior art, ethers such as tetrahydrofuran and/or complexing agents such as organomagnesium compounds have been added to increase the solubility of the lithium amide in solution. The presence of the ethers makes these solutions unstable and they decompose on standing in storage. The presence of magnesium compounds in the reaction and subsequent workup is undesirable because the possibility of lower reactivity and yields of desired products plus the more difficult workup due to the presence of the formed magnesium oxide which is highly insoluble and formed during washing.
Additionally, when tetrahydrofuran is used as the solvent it has been found necessary to limit the amount of tetrahydrofuran to no more than one mole for each mole of lithium amide in order to minimize degradation of the system.
U.S. Pat. No. 4,595,779 to Morrison et al relates to a composition and method for preparing lithium diisopropyl amide by the reaction of lithium metal and diisopropylamine in tetrahydrofuran and an inert liquid hydrocarbon cosolvent including styrene as an electron carrier. The use of tetrahydrofuran is considered essential in the preparation when utilizing lithium metal.
The article of Keith Smith entitled "Lithiation and Organic Synthesis", Chemistry In Britain, January 1982, pages 29-32, discloses the preparation of lithium dialkyl amides for use as lithiating agents by the reaction of organolithium reagents in aliphatic hydrocarbon solvents.
It is an object of the present invention to provide a lithium amide reagent compositions having greater amounts of the lithium amide in solution and not precipitate on standing.
It is a further object of the invention to provide a process for preparing stable lithium amides in higher concentrations in solution and in a hydrocarbon solvent which is stable and free of ethers.
It is understood that the lithium alkoxides used in the invention include the lithium sec-alkoxides and lithium tert-alkoxides having 4 to 20 carbon atoms. These lithium branched alkoxides include lithium isopropoxide, lithium isobutoxide, lithium sec-butoxide, lithium sec-pentoxide, lithium t-butoxide, lithium t-pentoxide, and the like.